This career transition award will provide the candidate with the opportunity to investigate new areas of research: mechanotransduction and mechanical stimulation for regenerating condylar cartilage of the temporomandibular joint (TMJ). The environment in the Dept. of Chemical and Biological Eng. at the University of Colorado and the School of Dentistry at the Health Science Center will provide the candidate with fruitful collaborations, mentorship and a plethora of shared equipment. The long-term goals of the candidate are (i) to develop a successful research career in tissue engineering, (ii) to make a substantial advancement in developing tissue engineering strategies for treating patients with TMJ disorders, and (iii) to provide a positive learning environment for the next generation of researchers and tissue engineers. The overall objective of this proposal is to stimulate the regeneration of cartilage through mechanical conditioning of tissue engineering scaffolds for the replacement of condylar cartilage of the TMJ. The global hypothesis of this research is photopolymerized gels can be designed with high fidelity to provide insight into the mechanotransduction pathways of chondrocytes, and this knowledge can then be used to engineer gel environments that when subjected to mechanical conditioning will promote functional tissue development. Specifically, the aims of this research are to: Aim 1: Elucidate the chondrocyte's response (cell proliferation and ECM synthesis) to a range of loading conditions as a function of gel material properties and chemistries; Aim 2: Isolate and study the mechanotransduction pathways in chondrocytes that involve nitric oxide and intracellular calcium and their potential role in the cell's response to changes in cell deformation and streaming potentials and to the presence of cell-ECM interactions. Aim 3: Incorporate degradable crosslinks into the hydrogels and examine the macroscopic tissue composition and mechanical properties as a function of loading regimes and degradation profiles.